Inclusion Criteria

• Documentation of Disease
  • Confirmation of GCT histology (both seminoma and nonseminoma) on pathologic review at the center of enrollment
  • Tumor may have originated in any primary site
    • In rare circumstances, patients will be allowed to enroll even if a pathologic diagnosis may not have been established
    • This would require a clinical situation consistent with the diagnosis of GCT (testicular, peritoneal, retroperitoneal or mediastinal mass, elevated tumor marker levels {HCG ≥ 500; AFP ≥ 500} and typical pattern of metastases)
• Evidence of Disease
  • Must have evidence of progressive or recurrent GCT (measurable or non-measurable) following one line of cisplatin-based chemotherapy, defined as meeting at least one of the following criteria
    • Tumor biopsy of new or growing or unresectable lesions demonstrating viable non-teratomatous GCT
      • Enrollment in this study for adjuvant treatment after macroscopically complete resection of viable GCT is not allowed
    • In the event of an incomplete gross resection where viable GCT is found, patients will be considered eligible for the study
    • Consecutive elevated serum tumor markers (HCG or AFP) that are increasing
      • Increase of an elevated LDH alone does not constitute progressive disease
    • Development of new or enlarging lesions in the setting of persistently elevated HCG or AFP, even if the HCG and AFP are not continuing to increase
• Prior Treatment
  • Must have received 3-6 cycles of cisplatin-based chemotherapy as part of first-line (initial) chemotherapy
    • Prior POMBACE, CBOP-BEP, or GAMEC are allowed
    • For patients requiring immediate treatment, 1 cycle of conventional-dose salvage chemotherapy is allowed
      • Therefore, these patients may have received 7 prior cycles of chemotherapy. 6 cycles as part of first-line chemotherapy and 1 cycle of salvage conventional chemotherapy
  • No more than one prior line of chemotherapy for GCT (other than the 1 cycle of salvage chemotherapy as defined in the protocol)
    • Definition of one line of chemotherapy: One line of therapy can in some cases consist of 2 different cisplatin-based treatment combinations, provided there is no disease progression between these two regimens
    • Prior treatment with carboplatin as adjuvant therapy is allowed, provided patients meet other eligibility criteria (e.g., the patient has also received 3-4 cycles of cisplatin-based chemotherapy)
    • Prior treatment with 1-2 cycles of BEP or EP as adjuvant chemotherapy for early stage GCT is allowed, provided the patient also received 3-4 cycles of BEP or EP again at relapse.
      • Patients treated with 3-4 cycles of VIP at relapse following 1-2 cycles of BEP/EP are not eligible as this would be considered more than 1 line of prior therapy
  • No prior treatment with high-dose chemotherapy (defined as treatment utilizing stem cell rescue)
  • No prior treatment with TIP with the exception when given as a bridge to treatment on protocol for patients with rapidly progressive disease who cannot wait to complete the eligibility screening process. Only one cycle is allowed.
  • No concurrent treatment with other cytotoxic drugs or targeted therapies
  • No radiation therapy (other than to the brain) within 14 days of day 1 of protocol chemotherapy except radiation to brain metastases, which must be completed 7 days prior to start of chemotherapy
  • No previous chemotherapy within 17 days prior to enrollment. A minimum of three weeks after the last day of the start of the previous chemotherapy regimen before the first day of chemotherapy on study protocol
  • Must have adequate recovery from prior surgery (eg, healed scar, resumption of diet)
• Age ≥ 14 years (≥ 18 years in Germany)
• ECOG performance status 0 to 2
• Male gender
• Required initial laboratory values
  • Absolute Neutrophil Count (ANC) ≥ 1,500/mm^3
  • Platelet Count ≥ 100,000/mm^3
  • Calculated creatinine clearance ≥ 50 mL/min
  • Bilirubin ≤ 2.0 x upper limits of normal (ULN)
  • AST/ALT ≤ 2.5 x upper limits of normal (ULN)
• No concurrent malignancy other than non-melanoma skin cancer, superficial noninvasive (pTa or pTis) TCC of the bladder, contralateral GCT, or intratubular germ cell neoplasia
  • Patients with a prior malignancy, but at least 2 years since any evidence of disease are allowed
• Negative Serology (antibody test) for the following infectious diseases
  • Human Immunodeficiency Virus (HIV) type 1 and 2
  • Human T-cell Leukemia Virus (HTLV) type 1 and 2 (mandatory in US but optional in Canada and Europe)
  • Hepatitis B surface antigen
  • Hepatitis C antibody
• No late relapse with completely surgically resectable disease
• Patients with late relapses defined as relapse ≥ 2 years from the date of completion of the last chemotherapy regimen whose disease is completely surgically resectable are not eligible
  • Patients with late relapses who have unresectable disease are eligible.
• No large (≥ 2 cm) hemorrhagic or symptomatic brain metastases until local treatment has been administered (radiation therapy or surgery)
  • Treatment may begin ≥ 7 days after completion of local treatment
  • Patients with small (< 2 cm) and asymptomatic brain metastases are allowed and may be treated with radiation therapy and/or surgery concurrently with Arm A or cycles 1 and 2 of Arm B if deemed medically indicated
• Radiation therapy should not be given concurrently with high-dose carboplatin or etoposide
• No secondary somatic malignancy arising from teratoma (e.g., teratoma with malignant transformation) when it is actively part of the disease recurrence or progression